Project Summary/Abstract: Over the past few decades, our knowledge of the mechanisms by which cells interact with drugs and toxins has exploded due to new molecular analysis techniques and the application of genomic methods. Accordingly, the emphasis of graduate education in the disciplines of pharmacology and toxicology needs to shift from a reductionist view to a systems approach in which doctoral students are comprehensively trained so they can formulate a strategy to solve important biological questions not only at the molecular, cellular, and tissue levels but also at the whole-animal level. Systems pharmacology and toxicology describes a field of study that considers the broad view of drug action. A systems approach using in vivo animal models is necessary to establish efficacy, safety and the pharmacodynamic/pharmacokinetic profile of candidate drugs but there is a shortage of students trained in this area. This Systems Pharmacology and Toxicology (SPaT) Program is designed for PhD students in their second year of graduate study pursuing dissertation research projects in the pharmacological sciences. Trainees (2/year for up to 2 years of support) and training faculty (30 mentors and 4 teachers) are drawn from the Graduate Program in Interdisciplinary Biomedical Sciences and the MD/PhD Program. The SPaT program will train students to use an in vivo approach to answering relevant questions in pharmacology and toxicology with emphasis on metabolism, drug design, pharmacodynamics, pharmacokinetics, and signaling. The rationale for SPaT is that this type of training provides students with a much broader perspective on pharmacology and toxicology that better prepares them to be leaders of multi-disciplinary research teams in the pharmacological sciences. We will integrate SPaT into PhD training programs already active at our graduate training sites in the Little Rock area that include faculty/scientists in the Colleges of Medicine, Pharmacy, and Public Health on the UAMS, the Arkansas Children's Hospital campus, and at the Food and Drug Administration-funded National Center for Toxicological Research. The unique focus of SPaT is training with in vivo systems pharmacological and toxicological approaches and concepts. The objective of SPaT is to provide in vivo pharmacology and toxicology training that complement the cellular and molecular training that students receive in their home programs. The training program consists of didactic training in pharmacology, toxicology, physiology, pharmacokinetics, metabolism, biostatistics, grant writing, and the Responsible Conduct of Research along with laboratory research using an in vivo model of human disease. The SPaT program will also provide strong mentoring, extensive networking, and teaching and leadership opportunities for its trainees through its programmatic activities.